Class II antigens (HLA-DR and HLS-DQ) are membrane bound glycoproteins encoded by genes in the major histocompatibility complex. In addition to their well established role as regulatory molecules of the immune respnse, these determinants are now suspected of playing an influencial part in cellular differentiation. In exploring the cellular composition of a popular childhood tumor, retinoblastoma, we have had an opportunity to describe class II antigens on a population of undifferentiated malignant cells of the retina. This study provides the initial description of calss II antigens on retinoblastoma cells. Furthermore, HLA-DR antigen was found to be coexpressed on cells that contained both neuronal and glial markers. This study also identifies for the first time the presence of class II angigens on cells of neuronal origin. Based on these initial studies, two areas will be explored. The first approach will focus on the possible role of class II antigens in the cellular differentiation or immune reactivity. The second will examine the prognostic significance of these molecules on retinoblastoma cells and the possible relationship class II proteins may have to the modulation and management of this tumor.